Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A

Abstract

Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the current study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using western blot. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis

“… 27 In addition, hsa_circ_0000144 sponged miR-623 to upregulate GPRC5A expression, so as to promote GC progression. 28 In keeping with former discoveries, we also detected the upregulation of hsa_circ_0000144 in GC tissues and cells, especially in OXA-resistant tissues and cells. The inhibitory influence of hsa_circ_0000144 knockdown on OXA resistance, proliferation and metastasis in OXA-resistant GC cells in vitro, as well as on tumor growth in vivo was disclosed.…”

GPRC5A: An emerging prognostic biomarker for predicting malignancy of Pancreatic Cancer based on bioinformatics analysis

“…The downstream activation of YAP by hypoxia required GPRC5A, which enabled hypoxic cell survival by suppressing apoptosis via BCL-XL induction 40 . Studies in gastric cancer also suggested that GPRC5A was an oncogene exerting its function by regulating EMT or the epidermal growth factor receptor (EGFR) signaling 44 , 45 . Sawada et al reported that in prostate cancer GPRC5A facilitated cell proliferation through cell cycle regulation and was significantly essential for bone metastasis 46 .…”

Identification of circRNA-miRNA-mRNA Regulatory Network in Bladder Cancer by Integrated Analysis

“…Hsa_circ_0000144 was reported to promote GC cell proliferation, migration, and invasion [34]. Mi et al [35] demonstrated circ-0000144 knockdown could repress GC progression by regulating GPRC5A expression via sponging miR-623. Significantly aberrant expressed hsa_ circ_0000144 was identified in BC in current study, which had been confirmed with qRT-PCR as well.…”